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General Principles of Cell Communication, Intracellular Signaling Pathway Activation by Extracellular Signal Molecule

Cell signaling is an intricate system of communication that coordinates cell actions and regulates basic cellular activity.
Cell signaling is an intricate system of communication that coordinates cell actions and regulates basic cellular activity. Cells can sense and respond to their microenvironment based upon their internal and external signals during development, tissue repair, immunity, and normal tissue homeostasis. Cancer and autoimmune diseases are often caused by errors during the information processing process. Understanding cell signaling can lead to effective treatments for diseases, and it may be possible, in theory, to generate artificial tissues.

Chemical signals are typically used by cells to communicate. Chemical signals made up of proteins and other molecules produced by cells are frequently secreted into the extracellular space by the cells sending them. They can then float over to neighboring cells - like a message in a bottle.

Chemical signals are not always recognized by all cells. The right receptor for a signal is required by a neighbor cell to detect that signal (that is, to be a target cell). In response to a signaling molecule binding to its receptor, the receptor changes its shape or activity, which causes a change inside the cell. Identifying ligands that are used as signaling molecules is a general term that refers to substances that bind to certain molecules. Messages transmitted by ligands in the cell are often relayed through a chain of chemical messengers.

Ultimately, it causes changes within the cell, for instance affecting the activity of a gene or initiating processes such as cell division. So, the original intercellular signal (between cells) becomes an intracellular signal (within cells) that triggers a response.

Signals resulting in an intracellular pathway that can be activated by extracellular molecules
Signal molecules most commonly bind to a protein in the PM of the target cells. Signaling proteins are activated as a result of the receptor activating one or more intracellular signaling pathways. The final component is that a certain number of intracellular signaling proteins affect the activity of effector proteins and, thus, the behavior of the cell.

Intercellular signaling has four forms
Extracellular messenger molecules are usually how cells communicate with one another.
  1. A cell must be in direct membrane-to-membrane contact for contact-dependent signaling to occur. Contact is essential for development as well as immune response.
  2. Paracrine signaling is dependent on the release of local mediators into the extracellular space and their action on nearby cells.
  3. Synaptic signaling is the transmission of electrical signals along axons by neurons and the release of neurotransmitters at synapses.
  4. Hormones secreted by endocrine cells are distributed throughout the body via the bloodstream by endocrine cells
Autocrine signaling - Signalling cells release their signal and are the target of the process. The survival of a cell may be impacted by multiple signals (A, B, C). D, E, F, G are additional signals of growth and division. If the cell is deprived of the appropriate survival signals, it undergoes apoptosis.

Specific receptors bind to extracellular signal molecules
  • A variety of extracellular signal molecules are involved in signal pathways, including proteins, amino acids, peptides, steroids, retinoids, fatty acid derivatives, nitrate, and carbon monoxide.
  • Cells respond to such molecules through receptors.
  • The receptors can be divided into two categories:
  1. Transmembrane proteins are the most common receptors on target cells. Signal transducers bind to extracellular molecules (ligands) and become activated as a result of signal transduction, causing a variety of intracellular signals which alter cellular behavior.
  2. Signal molecules must be small enough to diffuse across the PM and bind to receptor proteins inside the target cells, either in their nuclei or cytosol.

Signaling ligands types
To stimulate target cells to respond, chemically-signaled cells fix onto receptors in those cells
1. Small Hydrophobic Ligands
Molecular ligands with hydrophobic properties can directly bind to internal receptors through the plasma membrane. The steroid hormones constitute a significant part of this class of ligands.

2. Other Ligands
Gases such as nitric oxide (NO) may also serve as ligands. This protein interacts with receptors in smooth muscle and stimulates relaxation of that tissue via direct diffusion through the plasma membrane. It is short-lived, and therefore can only operate over short distances

3. Water-Soluble Ligands
The polar ligands that are water-soluble cannot pass the plasma membrane alone since they are polar. Rather than binding to intracellular receptors, most water-soluble ligands bind to extracellular ones. Most water-soluble ligands are attached to extracellular receptors, rather than intracellular ones. Ion-channels, G-proteins, and enzyme-linked proteins are among the cell-surface receptors. These ligands are bound to these receptors, leading to several changes in the cellular environment. In addition to small molecules, peptides, and proteins, water-soluble ligands have a variety of functions.
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Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
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